| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Moffat, Cynthia Bhatia, Lavesh Nguyen, Teresa Lynch, Peter Wang, Miao Wang, Dongning Ilkayeva, Olga R. Han, Xianlin Hirschey, Matthew D. Claypool, Steven M. Seifert, Erin L. |
| Description |
Author Affiliation: Moffat C ( Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.); Bhatia L ( Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.); Nguyen T ( Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.); Lynch P ( Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.); Wang M ( Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827.); Wang D ( Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710.); Ilkayeva OR ( Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710.); Han X ( Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827.); Hirschey MD ( Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710.); Claypool SM ( Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD 21205.); Seifert EL ( Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.) |
| Abstract |
Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxi-dative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpression in mouse liver (Ad-Acot2), we show that Acot2 increases the utilization of FA substrate during the daytime in ad libitum-fed mice, but the nighttime switch to carbohydrate oxidation is similar to control mice. In further support of elevated FAO in Acot2 liver, daytime serum ketones were higher in Ad-Acot2 mice, and overnight fasting led to minimal hepatic steatosis as compared with control mice. In liver mitochondria from Ad-Acot2 mice, phosphorylating O2 consumption was higher with lipid substrate, but not with nonlipid substrate. This increase depended on whether FA could be activated on the outer mitochondrial membrane, suggesting that the FA released by Acot2 could be effluxed from mitochondria then taken back up again for oxidation. This circuit would prevent the build-up of inhibitory long-chain fatty acyl-CoA esters. Altogether, our findings indicate that Acot2 can enhance FAO, possibly by mitigating the accumulation of FAO intermediates within the mitochondrial matrix. |
| File Format |
HTM / HTML |
| ISSN |
00222275 |
| e-ISSN |
15397262 |
| DOI |
10.1194/jlr.M046961 |
| Journal |
The Journal of Lipid Research |
| Issue Number |
12 |
| Volume Number |
55 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology |
| Publisher Date |
2014-12-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Biochemistry Acyl Coenzyme A Metabolism Energy Metabolism Fatty Acids, Nonesterified Liver Mitochondria, Liver Mitochondrial Proteins Palmitoyl-coa Hydrolase Thiolester Hydrolases Animals Carbohydrate Metabolism Cells, Cultured Circadian Rhythm Blood Ketone Bodies Kinetics Lipid Metabolism Cytology Ultrastructure Mice, Inbred C57bl Microscopy, Electron, Transmission Enzymology Genetics Oxidation-reduction Oxidative Phosphorylation Recombinant Proteins Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Endocrinology |
